1. Neurobiology of Learning and Memory
Prof. Stephan Anagnostaras
Lecture 3: HM, the medial temporal lobe, and amnesia

2. Serial model Can test these models in brain damaged subjects
Memory terminology based on information processing models
e.g., Serial Model
Can test these models in brain damaged subjects

3. Amnesia
Amnesia Partial or total loss of memory, usually resulting from shock, psychological disturbance, brain injury, or illness.
Organic caused by shock, brain injury, illness • hypoxic episode, herpes encephalitis • epilepsy, brain injury, Alzheimer’s disease
Psychogenic caused by psychological trauma • dissociative disorders • psychogenic fugue • multiple personality disorder

4. Amnesia Amnesia can be global or material-specific
Global any kind of information is affected
Material-specific certain kinds of material (e.g., faces)
Amnesia can be anterograde or retrograde
Anterograde amnesia inability to learn anything new since the time of the trauma (usually organic)
Retrograde amnesia loss of memory for events prior to the time of the trauma (psychogenic or organic)

5. HM Most famous case reported by Scoville & Milner (1957)
Scoville did the surgeries for psychosis but didn’t work, so tried it for epilepsy on about 30 patients. Patients studied by Brenda Milner
HM: bilateral medial temporal lobe lesion for status epilepticus in 1953

6. HM’s lesion: bilateral medial temporal lobe removal

7. HM = no hippocampus, amygdala, overlying (rhinal) cortex
normal
hpc
HM = no hpc, no rhinal ctx

8. HM = no hippocampus, amygdala, overlying (rhinal) cortex

9. HM’s amnesic syndrome
Severe deficit (global anterograde amnesia) • show word or face, ask later, doesn’t know • reads newspapers repeatedly • doesn’t remember own physician
• see on formal tests or everyday life • word lists • faces and objects • recall or recognition
Only mild retrograde amnesia • loss of memories that are a up to 2-3 years old at the time of the lesion, but childhood memories in tact • known as a time-limited or temporally-graded retrograde amnesia

10. Retrograde vs. anterograde amnesia
normal memory
for remote events
(childhood, etc)
for HM, retrograde amnesia
is approx. 2 yrs
Retrograde and anterograde
amnesia can occur together
or separately (HM has both)
HM also has this

11. Remote versus Recent Memory: HM, Loss of Recent memory

12. Medial temporal lobe amnesia: what’s special?
Deficit very specific for Long-Term Memory (LTM)
• not dementia
• IQ normal and unchanged
• perceptual skills excellent
• social skills and personality intact
• Short-Term Memory (STM = 3 min, 7±2 items) good (e.g., digit span)
• forgetting curve for STM normal
• Memory scale more than 3 std dev from controls!

13. Rey-Osterrieth Figure

14. Rey-Osterrieth Figure

15. Famous Faces test of explicit memory and retrograde amnesia NF = non-famous (control)
madeline albright c. everitt koop ladybird johnson
normal schwarzkopf geraldine feraro jim belushi joni mitchell

16. Retrograde amnesia often shows a gradient: memory for older events (1950’s) is better than memory for newer events (1980’s)
Amnesics worse than controls
Damage to hpc = Memory that was still in hpc “buffer”got lost
before it could be consolidated into permanent memory
elsewhere in the brain

17. Spared learning
Learns some things normally: • visual motor pursuit • priming
• mirror drawing task • normal eyeblink classical conditioning (e.g., puff of air/tone on eye but not fear)
• but doesn’t ever remember doing task before (source amnesia)
These tasks do not necessarily share anything in common.

18. HM could improve on task but didn’t recognize task each day
Fig.
14.4

19. HM improved in performance despite not remembering the test
Fig.
14.6
madeline albright c. everitt koop ladybird johnson
normal schwarzkopf geraldine feraro jim belushi joni mitchell

20. remember word list well
Repetition Priming: Testing Implicit Memory (Graf et al., 1984)
But they still can
complete the fragment
with the previously
seen word
First the list:
Then complete the word:
Amnesics don’t
remember word list well
ABSENT ABS__________
INCOME INC__________
FILLY FIL__________
DISCUSS DIS__________
CHEESE CHE__________
ELEMENT ELE__________
• free recall
• cued recall: complete word stem with specific word from study list
abs____ ??
• word stem completion: complete word stem with first word that
comes to mind
dis___??
• same cue in cued recall & word-stem
completion but only cued recall requires
conscious access to past
madeline albright c. everitt koop ladybird johnson
normal schwarzkopf geraldine feraro jim belushi joni mitchell

21. Mirror Reading

22. Some spatial memory

23. Explicit versus Implicit Memory
Memory impacted by the lesion termed explicit (or declarative) memory - must be stated verbally and requires conscious recollection (note: doesn’t work for animals) -includes semantic (facts, knowledge) and episodic (events, memory) memory
Not disrupted: implicit memory (procedural or nondeclarative) - learning is demonstrated through performance and may not be available to verbal recollection (e.g., tying your shoelaces)
Note that implicit memory is a junk term that includes several different forms of memory, including most forms of classical conditioning

24. Neuroanatomy
• The hippocampus is the critical structure for explicit memory Patient RB: damage only to CA1
• Disruption of hippocampal-circuitry can give a similar deficit (dorsomedial thamalus)
• The greater the disruption to surrounding cortex the more severe the amnesia
• Anterograde and retrograde amnesia usually correlated (HM is an exception)

25. (diencephalon area of brain) (Korsakoff’s and Pt N.A.)
More selective brain damage can produce explicit memory problems (amnesia), also
Korsakoff’s amnesia:
damage to MD thalamus
(diencephalon area of brain)
madeline albright c. everitt koop ladybird johnson
normal schwarzkopf geraldine feraro jim belushi joni mitchell
Pt R.B.:
damage to
CA1 area of hpc
(very selective)
medial diencephalic
amnesia
(Korsakoff’s and Pt N.A.)
Zola-Morgan, Squire, & Amaral, 1986

26. RB’s brain

27. Herpes encephalitis Normal Herpes Simplex Encephalitis
Reed & Squire (1998)

28. Alzheimer’s disease: plaques & tangles in memory areas
•severe and more general memory loss
(explicit + verbal implicit, e.g., priming)
•affects entorhinal ctx (1), then hpc (2), frontal (3),
parietal (3) lobes

29. Other forms of amnesia
Unilateral hippocampal damage results in material-specific deficits left = words, names, etc. right = faces, objects, etc.
Korsakoff’s psychosis results in similar amnesia plus confabulation
Frontal lobes STM, working memory, temporal order, confabulation
Electroconvulsive Therapy (ECT,ECS)

30. Multiple memory systems in the brain
Explicit memory
Implicit memory
Medial temporal lobe; diencephalon
Priming
(neocortex)
Classical conditioning
Events
(episodic)
Procedural memory:
skills & habits
(basal ganglia)
Facts
(semantic)
Emotional Responses
(amygdala)
Skeletal musculature
(cerebellum)
Eyeblink conditioning in rabbit

31. HM normal on this? Explicit or Implicit learning?
madeline albright c. everitt koop ladybird johnson
normal schwarzkopf geraldine feraro jim belushi joni mitchell

32. Classical (Pavlovian) conditioning and memory
There are many different forms of classical conditioning and the responsible brain structure depends on the form
Examples:
a) Pavlovian fear conditioning: Tone --> Shock Then: Tone --> freeze (CS) (US) (CS) (CR)
• Depends on the amygdala
• + the hippocampus with trace procedure
• + the hippocampus if the CS is a context
Eyeblink conditioning Tone --> puff of air to eye Then: Tone --> eyeblink (CS) (US) (CS) (CR)
•Depends on cerebellum
• + hippocampus with trace procedure
• Declarative knowledge of task always depends on hippocampus